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2. Generation of a gene-edited H9 embryonic stem cell line carrying a DOX-inducible NGN2 expression cassette in the CLYBL locus.

Author

Miellet, S, St Clair-Glover, M, Maddock, M, Dottori, M, Miellet, S, St Clair-Glover, M, Maddock, M, and Dottori, M

Abstract

The pro-neural transcription factor neurogenin-2 (NGN2) possesses the ability to rapidly and effectively transform stem cells into fully operational neurons. Here we report the successful generation of a modified H9 human embryonic H9 stem cell line containing a doxycycline (DOX) inducible NGN2 expression construct featuring a floxed Blasticidin/mApple selection module in the safe-harbor locus CLYBL. This cell line retains its pluripotent state in the absence of DOX, yet readily transitions into a neuronal state upon DOX introduction.

Published
2024

3. Organization and Activity of Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging

Author

Ciampi, Q, Pepi, M, Antonini-Canterin, F, Barbieri, A, Barchitta, A, Faganello, G, Miceli, S, Parato, V, Tota, A, Trocino, G, Abbate, M, Accadia, M, Alemanni, R, Angelini, A, Anglano, F, Anselmi, M, Aquila, I, Aramu, S, Avogadri, E, Azzaro, G, Badano, L, Balducci, A, Ballocca, F, Barbarossa, A, Barbati, G, Barletta, V, Barone, D, Becherini, F, Benfari, G, Beraldi, M, Bergandi, G, Bilardo, G, Binno, S, Bolognesi, M, Bongiovi, S, Bragato, R, Braggion, G, Brancaleoni, R, Bursi, F, Dessalvi, C, Cameli, M, Canu, A, Capitelli, M, Capra, A, Carbonara, R, Carbone, M, Carbonella, M, Carrabba, N, Casavecchia, G, Casula, M, Chesi, E, Cicco, S, Citro, R, Cocchia, R, Colombo, B, Colonna, P, Conte, M, Corrado, G, Cortesi, P, Cortigiani, L, Costantino, M, Cozza, F, Cucchini, U, D'Angelo, M, Ros, S, D'Andrea, F, D'Andrea, A, D'Auria, F, De Caridi, G, De Feo, S, De Matteis, G, De Vecchi, S, Del Giudice, C, Dell'Angela, L, Delli Paoli, L, Dentamaro, I, Destefanis, P, Di Fulvio, M, Di Gaetano, R, Di Giannuario, G, Di Gioia, A, Di Martino, L, Di Muro, C, Di Nora, C, Di Salvo, G, Dodi, C, Dogliani, S, Donati, F, Dottori, M, Epifani, G, Fabiani, I, Ferrara, F, Ferrara, L, Ferrua, S, Filice, G, Fiorino, M, Forno, D, Garini, A, Giarratana, G, Gigantino, G, Giorgi, M, Giubertoni, E, Greco, C, Grigolato, M, Marra, W, Holzl, A, Iaiza, A, Iannaccone, A, Ilardi, F, Imbalzano, E, Inciardi, R, Inserra, C, Iori, E, Izzo, A, La Rosa, G, Labanti, G, Lanzone, A, Lanzoni, L, Lapetina, O, Leiballi, E, Librera, M, Lo Conte, C, Lo Monaco, M, Lombardo, A, Luciani, M, Lusardi, P, Magnante, A, Malagoli, A, Malatesta, G, Mancusi, C, Manes, M, Manganelli, F, Mantovani, F, Manuppelli, V, Marchese, V, Marinacci, L, Mattioli, R, Maurizio, C, Mazza, G, Mazza, S, Melis, M, Meloni, G, Merli, E, Milan, A, Minardi, G, Monaco, A, Monte, I, Montresor, G, Moreo, A, Mori, F, Morini, S, Moro, C, Morrone, D, Negri, F, Nipote, C, Nisi, F, Nocco, S, Novello, L, Nunziata, L, Perini, A, Parodi, A, Pasanisi, E, Pastorini, G, Pavasini, R, Pavoni, D, Pedone, C, Pelliccia, F, Pelliciari, G, Pelloni, E, Pergola, V, Perillo, G, Petruccelli, E, Pezzullo, C, Piacentini, G, Picardi, E, Pinna, G, Pizzarelli, M, Pizzuti, A, Poggi, M, Posteraro, A, Privitera, C, Rampazzo, D, Ratti, C, Rettegno, S, Ricci, F, Ricci, C, Rolando, C, Rossi, S, Rovera, C, Ruggieri, R, Russo, M, Sacchi, N, Saladino, A, Sani, F, Sartori, C, Scarabeo, V, Sciacqua, A, Scillone, A, Scopelliti, P, Scorza, A, Scozzafava, A, Serafini, F, Serra, W, Severino, S, Simeone, B, Sirico, D, Solari, M, Spadaro, G, Stefani, L, Strangio, A, Surace, F, Tamborini, G, Tarquinio, N, Tassone, E, Tavarozzi, I, Tchana, B, Tedesco, G, Tinto, M, Torzillo, D, Totaro, A, Triolo, O, Troisi, F, Tusa, M, Vancheri, F, Varasano, V, Venezia, A, Vermi, A, Villari, B, Zampi, G, Zannoni, J, Zito, C, Zugaro, A, Di Bella, G, Carerj, S, Ciampi Q., Pepi M., Antonini-Canterin F., Barbieri A., Barchitta A., Faganello G., Miceli S., Parato V. M., Tota A., Trocino G., Abbate M., Accadia M., Alemanni R., Angelini A., Anglano F., Anselmi M., Aquila I., Aramu S., Avogadri E., Azzaro G., Badano L., Balducci A., Ballocca F., Barbarossa A., Barbati G., Barletta V., Barone D., Becherini F., Benfari G., Beraldi M., Bergandi G., Bilardo G., Binno S. M., Bolognesi M., Bongiovi S., Bragato R. M., Braggion G., Brancaleoni R., Bursi F., Dessalvi C. C., Cameli M., Canu A., Capitelli M., Capra A. C. M., Carbonara R., Carbone M., Carbonella M., Carrabba N., Casavecchia G., Casula M., Chesi E., Cicco S., Citro R., Cocchia R., Colombo B. M., Colonna P., Conte M., Corrado G., Cortesi P., Cortigiani L., Costantino M. F., Cozza F., Cucchini U., D'Angelo M., Ros S. D., D'Andrea F., D'Andrea A., D'Auria F., De Caridi G., De Feo S., De Matteis G. M., De Vecchi S., Del Giudice C., Dell'Angela L., Delli Paoli L., Dentamaro I., Destefanis P., Di Fulvio M., Di Gaetano R., Di Giannuario G., Di Gioia A., Di Martino L. F. M., Di Muro C., Di Nora C., Di Salvo G., Dodi C., Dogliani S., Donati F., Dottori M., Epifani G., Fabiani I., Ferrara F., Ferrara L., Ferrua S., Filice G., Fiorino M., Forno D., Garini A., Giarratana G. A., Gigantino G., Giorgi M., Giubertoni E., Greco C. A., Grigolato M., Marra W. G., Holzl A., Iaiza A., Iannaccone A., Ilardi F., Imbalzano E., Inciardi R., Inserra C. A., Iori E., Izzo A., La Rosa G., Labanti G., Lanzone A. M., Lanzoni L., Lapetina O., Leiballi E., Librera M., Lo Conte C., Lo Monaco M., Lombardo A., Luciani M., Lusardi P., Magnante A., Malagoli A., Malatesta G., Mancusi C., Manes M. T., Manganelli F., Mantovani F., Manuppelli V., Marchese V., Marinacci L., Mattioli R., Maurizio C., Mazza G. A., Mazza S., Melis M., Meloni G., Merli E., Milan A., Minardi G., Monaco A., Monte I., Montresor G., Moreo A., Mori F., Morini S., Moro C., Morrone D., Negri F., Nipote C., Nisi F., Nocco S., Novello L., Nunziata L., Perini A. P., Parodi A., Pasanisi E. M., Pastorini G., Pavasini R., Pavoni D., Pedone C., Pelliccia F., Pelliciari G., Pelloni E., Pergola V., Perillo G., Petruccelli E., Pezzullo C., Piacentini G., Picardi E., Pinna G., Pizzarelli M., Pizzuti A., Poggi M. M., Posteraro A., Privitera C., Rampazzo D., Ratti C., Rettegno S., Ricci F., Ricci C., Rolando C., Rossi S., Rovera C., Ruggieri R., Russo M. G., Sacchi N., Saladino A., Sani F., Sartori C., Scarabeo V., Sciacqua A., Scillone A., Scopelliti P. A., Scorza A., Scozzafava A., Serafini F., Serra W., Severino S., Simeone B., Sirico D., Solari M., Spadaro G. L., Stefani L., Strangio A., Surace F. C., Tamborini G., Tarquinio N., Tassone E. J., Tavarozzi I., Tchana B., Tedesco G., Tinto M., Torzillo D., Totaro A., Triolo O. F., Troisi F., Tusa M., Vancheri F., Varasano V., Venezia A., Vermi A. C., Villari B., Zampi G., Zannoni J., Zito C., Zugaro A., Di Bella G., Carerj S., Ciampi, Q, Pepi, M, Antonini-Canterin, F, Barbieri, A, Barchitta, A, Faganello, G, Miceli, S, Parato, V, Tota, A, Trocino, G, Abbate, M, Accadia, M, Alemanni, R, Angelini, A, Anglano, F, Anselmi, M, Aquila, I, Aramu, S, Avogadri, E, Azzaro, G, Badano, L, Balducci, A, Ballocca, F, Barbarossa, A, Barbati, G, Barletta, V, Barone, D, Becherini, F, Benfari, G, Beraldi, M, Bergandi, G, Bilardo, G, Binno, S, Bolognesi, M, Bongiovi, S, Bragato, R, Braggion, G, Brancaleoni, R, Bursi, F, Dessalvi, C, Cameli, M, Canu, A, Capitelli, M, Capra, A, Carbonara, R, Carbone, M, Carbonella, M, Carrabba, N, Casavecchia, G, Casula, M, Chesi, E, Cicco, S, Citro, R, Cocchia, R, Colombo, B, Colonna, P, Conte, M, Corrado, G, Cortesi, P, Cortigiani, L, Costantino, M, Cozza, F, Cucchini, U, D'Angelo, M, Ros, S, D'Andrea, F, D'Andrea, A, D'Auria, F, De Caridi, G, De Feo, S, De Matteis, G, De Vecchi, S, Del Giudice, C, Dell'Angela, L, Delli Paoli, L, Dentamaro, I, Destefanis, P, Di Fulvio, M, Di Gaetano, R, Di Giannuario, G, Di Gioia, A, Di Martino, L, Di Muro, C, Di Nora, C, Di Salvo, G, Dodi, C, Dogliani, S, Donati, F, Dottori, M, Epifani, G, Fabiani, I, Ferrara, F, Ferrara, L, Ferrua, S, Filice, G, Fiorino, M, Forno, D, Garini, A, Giarratana, G, Gigantino, G, Giorgi, M, Giubertoni, E, Greco, C, Grigolato, M, Marra, W, Holzl, A, Iaiza, A, Iannaccone, A, Ilardi, F, Imbalzano, E, Inciardi, R, Inserra, C, Iori, E, Izzo, A, La Rosa, G, Labanti, G, Lanzone, A, Lanzoni, L, Lapetina, O, Leiballi, E, Librera, M, Lo Conte, C, Lo Monaco, M, Lombardo, A, Luciani, M, Lusardi, P, Magnante, A, Malagoli, A, Malatesta, G, Mancusi, C, Manes, M, Manganelli, F, Mantovani, F, Manuppelli, V, Marchese, V, Marinacci, L, Mattioli, R, Maurizio, C, Mazza, G, Mazza, S, Melis, M, Meloni, G, Merli, E, Milan, A, Minardi, G, Monaco, A, Monte, I, Montresor, G, Moreo, A, Mori, F, Morini, S, Moro, C, Morrone, D, Negri, F, Nipote, C, Nisi, F, Nocco, S, Novello, L, Nunziata, L, Perini, A, Parodi, A, Pasanisi, E, Pastorini, G, Pavasini, R, Pavoni, D, Pedone, C, Pelliccia, F, Pelliciari, G, Pelloni, E, Pergola, V, Perillo, G, Petruccelli, E, Pezzullo, C, Piacentini, G, Picardi, E, Pinna, G, Pizzarelli, M, Pizzuti, A, Poggi, M, Posteraro, A, Privitera, C, Rampazzo, D, Ratti, C, Rettegno, S, Ricci, F, Ricci, C, Rolando, C, Rossi, S, Rovera, C, Ruggieri, R, Russo, M, Sacchi, N, Saladino, A, Sani, F, Sartori, C, Scarabeo, V, Sciacqua, A, Scillone, A, Scopelliti, P, Scorza, A, Scozzafava, A, Serafini, F, Serra, W, Severino, S, Simeone, B, Sirico, D, Solari, M, Spadaro, G, Stefani, L, Strangio, A, Surace, F, Tamborini, G, Tarquinio, N, Tassone, E, Tavarozzi, I, Tchana, B, Tedesco, G, Tinto, M, Torzillo, D, Totaro, A, Triolo, O, Troisi, F, Tusa, M, Vancheri, F, Varasano, V, Venezia, A, Vermi, A, Villari, B, Zampi, G, Zannoni, J, Zito, C, Zugaro, A, Di Bella, G, Carerj, S, Ciampi Q., Pepi M., Antonini-Canterin F., Barbieri A., Barchitta A., Faganello G., Miceli S., Parato V. M., Tota A., Trocino G., Abbate M., Accadia M., Alemanni R., Angelini A., Anglano F., Anselmi M., Aquila I., Aramu S., Avogadri E., Azzaro G., Badano L., Balducci A., Ballocca F., Barbarossa A., Barbati G., Barletta V., Barone D., Becherini F., Benfari G., Beraldi M., Bergandi G., Bilardo G., Binno S. M., Bolognesi M., Bongiovi S., Bragato R. M., Braggion G., Brancaleoni R., Bursi F., Dessalvi C. C., Cameli M., Canu A., Capitelli M., Capra A. C. M., Carbonara R., Carbone M., Carbonella M., Carrabba N., Casavecchia G., Casula M., Chesi E., Cicco S., Citro R., Cocchia R., Colombo B. M., Colonna P., Conte M., Corrado G., Cortesi P., Cortigiani L., Costantino M. F., Cozza F., Cucchini U., D'Angelo M., Ros S. D., D'Andrea F., D'Andrea A., D'Auria F., De Caridi G., De Feo S., De Matteis G. M., De Vecchi S., Del Giudice C., Dell'Angela L., Delli Paoli L., Dentamaro I., Destefanis P., Di Fulvio M., Di Gaetano R., Di Giannuario G., Di Gioia A., Di Martino L. F. M., Di Muro C., Di Nora C., Di Salvo G., Dodi C., Dogliani S., Donati F., Dottori M., Epifani G., Fabiani I., Ferrara F., Ferrara L., Ferrua S., Filice G., Fiorino M., Forno D., Garini A., Giarratana G. A., Gigantino G., Giorgi M., Giubertoni E., Greco C. A., Grigolato M., Marra W. G., Holzl A., Iaiza A., Iannaccone A., Ilardi F., Imbalzano E., Inciardi R., Inserra C. A., Iori E., Izzo A., La Rosa G., Labanti G., Lanzone A. M., Lanzoni L., Lapetina O., Leiballi E., Librera M., Lo Conte C., Lo Monaco M., Lombardo A., Luciani M., Lusardi P., Magnante A., Malagoli A., Malatesta G., Mancusi C., Manes M. T., Manganelli F., Mantovani F., Manuppelli V., Marchese V., Marinacci L., Mattioli R., Maurizio C., Mazza G. A., Mazza S., Melis M., Meloni G., Merli E., Milan A., Minardi G., Monaco A., Monte I., Montresor G., Moreo A., Mori F., Morini S., Moro C., Morrone D., Negri F., Nipote C., Nisi F., Nocco S., Novello L., Nunziata L., Perini A. P., Parodi A., Pasanisi E. M., Pastorini G., Pavasini R., Pavoni D., Pedone C., Pelliccia F., Pelliciari G., Pelloni E., Pergola V., Perillo G., Petruccelli E., Pezzullo C., Piacentini G., Picardi E., Pinna G., Pizzarelli M., Pizzuti A., Poggi M. M., Posteraro A., Privitera C., Rampazzo D., Ratti C., Rettegno S., Ricci F., Ricci C., Rolando C., Rossi S., Rovera C., Ruggieri R., Russo M. G., Sacchi N., Saladino A., Sani F., Sartori C., Scarabeo V., Sciacqua A., Scillone A., Scopelliti P. A., Scorza A., Scozzafava A., Serafini F., Serra W., Severino S., Simeone B., Sirico D., Solari M., Spadaro G. L., Stefani L., Strangio A., Surace F. C., Tamborini G., Tarquinio N., Tassone E. J., Tavarozzi I., Tchana B., Tedesco G., Tinto M., Torzillo D., Totaro A., Triolo O. F., Troisi F., Tusa M., Vancheri F., Varasano V., Venezia A., Vermi A. C., Villari B., Zampi G., Zannoni J., Zito C., Zugaro A., Di Bella G., and Carerj S.

Abstract

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories: 112 centers (49%) in the northern, 43 centers (19%) in the central, and 73 (32%) in the southern regions. During the month of observation, we collected 101,050 transthoracic echocardiography (TTE) examinations performed in all centers. As concern other modalities there were performed 5497 transesophageal echocardiography (TEE) examinations in 161/228 centers (71%); 4057 stress echocardiography (SE) examinations in 179/228 centers (79%); and examinations with ultrasound contrast agents (UCAs) in 151/228 centers (66%). We did not find significant regional variations between the different modalities. The usage of picture archiving and communication system (PACS) was significantly higher in the northern (84%) versus central (49%) and southern (45%) centers (P < 0.001). Lung ultrasound (LUS) was performed in 154 centers (66%), without difference between cardiology and noncardiology centers. The evaluation of left ventricular (LV) ejection fraction was evaluated mainly using the qualitative method in 223 centers (94%), occasionally with the Simpson method in 193 centers (85%), and with selective use of the three-dimensional (3D) method in only 23 centers (10%). 3D TTE was present in 137 centers (70%), and 3D TEE in all centers where TEE was done (71%). The assessment of LV diastolic function was done routinely in 80% of the centers. Right ventricular function was evaluated using tricuspid annular plane systolic excursion in all centers, using tricuspid valve annular systolic velocity by tissue

Published
2023

5. Patient-specific iPSCs Reveal Vascular Dysfunction in Friedreich Ataxia

Author

Lees, J., primary, Zhang, N., additional, Kong, A., additional, Treller, A., additional, Mitchell, G., additional, Dottori, M., additional, Pebay, A., additional, Wilcox, S., additional, Chong, M., additional, Peverill, R., additional, Delatyki, M., additional, Pullin, J., additional, McCarthy, D., additional, Napierala, M., additional, and Lim, S., additional

Published
2023
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6. C55 A GIANT PSEUDOANEURYSM OF MITRAL–AORTIC INTERVALVULAR FIBROSA PRESENTING AS RECENT–ONSET ANGINA AND CARDIAC ARREST DUE TO VENTRICULAR FIBRILLATION

Author

Tofoni, P, primary, Patani, F, additional, Vagnarelli, F, additional, Lofiego, C, additional, Capodaglio, I, additional, Dottori, M, additional, Angelini, L, additional, Francioni, M, additional, Bonanni, C, additional, Grossi, P, additional, Galeazzi, M, additional, D‘Alfonso, A, additional, Marini, M, additional, Di Eusanio, M, additional, and Perna, G, additional

Published
2023
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8. Vulnerability to microplastic contamination in the Santos Estuarine System (Brazil) under extreme conditions of sea surface height

Author

Dialectaquiz, A., Sasaki, D., Silva, D., and Dottori, M.

Abstract

The accumulation and export of microplastics compose growing negative socio-environmental impacts, which are intensified in coastal and estuarine areas. The Santos Estuarine System set the most populous estuarine region, and with the largest seaport in Brazil, where the movement and accumulation of microplastics is an integrated effect of diverse hydrodynamic conditions. In order to identify the vulnerability of pollution by microplastics, in extreme conditions of elevation and depression of the sea surface in this complex estuarine region, the coupling between Lagrangian and Eulerian modeling was used, an approach that has become popular in the study of movements in the ocean. The trajectories of microplastics from potential sources were modeled using Opendrift, forced by currents from the Eulerian model ECOM, and waves from Wavewatch III. Particle concentrations and three-dimensional stochastic probability of contact with the continent were evaluated, demonstrating that, regardless of the sea surface elevation condition, microplastics are more exported to the South Brazilian Bight than accumulated on the margins and/or bottom of the system. During higher elevations of the sea surface there is greater accumulation of microplastics on the estuary margins, especially in neap tide, but with spring promoting faster transport. Although the entire coastline of Santos and adjacent beaches are prone to the largest accumulations, portions further to the Northeast of the estuary have not shown propensity to be contaminated with microplastics released into estuarine channels. The highest concentrations are actively drifting in the system's water column. This approach used is a pioneer in Brazilian estuarine systems., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Published
2023
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9. Making neurons, made easy: The use of Neurogenin-2 in neuronal differentiation

Author

Hulme, AJ, Maksour, S, Glover, MS-C, Miellet, S, Dottori, M, Hulme, AJ, Maksour, S, Glover, MS-C, Miellet, S, and Dottori, M

Abstract

Directed neuronal differentiation of human pluripotent stem cells (hPSCs), neural progenitors, or fibroblasts using transcription factors has allowed for the rapid and highly reproducible differentiation of mature and functional neurons. Exogenous expression of the transcription factor Neurogenin-2 (NGN2) has been widely used to generate different populations of neurons, which have been used in neurodevelopment studies, disease modeling, drug screening, and neuronal replacement therapies. Could NGN2 be a "one-glove-fits-all" approach for neuronal differentiations? This review summarizes the cellular roles of NGN2 and describes the applications and limitations of using NGN2 for the rapid and directed differentiation of neurons.

Published
2022

10. Transgene and Chemical Transdifferentiation of Somatic Cells for Rapid and Efficient Neurological Disease Cell Models.

Author

Ng, N, Newbery, M, Maksour, S, Dottori, M, Sluyter, R, Ooi, L, Ng, N, Newbery, M, Maksour, S, Dottori, M, Sluyter, R, and Ooi, L

Abstract

For neurological diseases, molecular and cellular research relies on the use of model systems to investigate disease processes and test potential therapeutics. The last decade has witnessed an increase in the number of studies using induced pluripotent stem cells to generate disease relevant cell types from patients. The reprogramming process permits the generation of a large number of cells but is potentially disadvantaged by introducing variability in clonal lines and the removal of phenotypes of aging, which are critical to understand neurodegenerative diseases. An under-utilized approach to disease modeling involves the transdifferentiation of aged cells from patients, such as fibroblasts or blood cells, into various neural cell types. In this review we discuss techniques used for rapid and efficient direct conversion to neural cell types. We examine the limitations and future perspectives of this rapidly advancing field that could improve neurological disease modeling and drug discovery.

Published
2022

12. Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

Author

Maucksch C, Firmin E, Butler-Munro C, Montgomery JM, Dottori M, and Connor B

Subjects
Adult human fibroblast cells, induced neural precursor cells, PAX6, somatic cell reprogramming, SOX2, Medicine, Medicine (General), R5-920
Abstract

Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP) colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP)-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

Published
2012

17. Development of Functional Thyroid C Cell-like Cells from Human Pluripotent Cells in 2D and in 3D Scaffolds

Author

Abu-Bonsrah, KD, Newgreen, DF, Dottori, M, Abu-Bonsrah, KD, Newgreen, DF, and Dottori, M

Abstract

Medullary thyroid carcinoma contributes to about 3-4% of thyroid cancers and affects C cells rather than follicular cells. Thyroid C cell differentiation from human pluripotent stem cells has not been reported. We report the stepwise differentiation of human embryonic stem cells into thyroid C cell-like cells through definitive endoderm and anterior foregut endoderm and ultimobranchial body-like intermediates in monolayer and 3D Matrigel culture conditions. The protocol involved sequential treatment with interferon/transferrin/selenium/pyruvate, foetal bovine serum, and activin A, then IGF-1 (Insulin-like growth factor 1), on the basis of embryonic thyroid developmental sequence. As well as expressing C cell lineage relative to follicular-lineage markers by qPCR (quantitative polymerase chain reaction) and immunolabelling, these cells by ELISA (enzyme-linked immunoassay) exhibited functional properties in vitro of calcitonin storage and release of calcitonin on calcium challenge. This method will contribute to developmental studies of the human thyroid gland and facilitate in vitro modelling of medullary thyroid carcinoma and provide a valuable platform for drug screening.

Published
2021

18. Abnormalities of mitochondrial dynamics and bioenergetics in neuronal cells from CDKL5 deficiency disorder

Author

Van Bergen, NJ, Massey, S, Stait, T, Ellery, M, Reljic, B, Formosa, LE, Quigley, A, Dottori, M, Thorburn, D, Stroud, DA, Christodoulou, J, Van Bergen, NJ, Massey, S, Stait, T, Ellery, M, Reljic, B, Formosa, LE, Quigley, A, Dottori, M, Thorburn, D, Stroud, DA, and Christodoulou, J

Abstract

CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental disorder caused by pathogenic variants in the Cyclin-dependent kinase-like 5 (CDKL5) gene, resulting in dysfunctional CDKL5 protein. It predominantly affects females and causes seizures in the first few months of life, ultimately resulting in severe intellectual disability. In the absence of targeted therapies, treatment is currently only symptomatic. CDKL5 is a serine/threonine kinase that is highly expressed in the brain, with a critical role in neuronal development. Evidence of mitochondrial dysfunction in CDD is gathering, but has not been studied extensively. We used human patient-derived induced pluripotent stem cells with a pathogenic truncating mutation (p.Arg59*) and CRISPR/Cas9 gene-corrected isogenic controls, differentiated into neurons, to investigate the impact of CDKL5 mutation on cellular function. Quantitative proteomics indicated mitochondrial defects in CDKL5 p.Arg59* neurons, and mitochondrial bioenergetics analysis confirmed decreased activity of mitochondrial respiratory chain complexes. Additionally, mitochondrial trafficking velocity was significantly impaired, and there was a higher percentage of stationary mitochondria. We propose mitochondrial dysfunction is contributing to CDD pathology, and should be a focus for development of targeted treatments for CDD.

Published
2021

19. In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia

Author

Viventi, S, Frausin, S, Howden, SE, Lim, SY, Finol-Urdaneta, RK, McArthur, JR, Abu-Bonsrah, KD, Ng, W, Ivanusic, J, Thompson, L, Dottori, M, Viventi, S, Frausin, S, Howden, SE, Lim, SY, Finol-Urdaneta, RK, McArthur, JR, Abu-Bonsrah, KD, Ng, W, Ivanusic, J, Thompson, L, and Dottori, M

Abstract

Friedreich ataxia (FRDA) is an autosomal recessive disease characterized by degeneration of dorsal root ganglia (DRG) sensory neurons, which is due to low levels of the mitochondrial protein Frataxin. To explore cell replacement therapies as a possible approach to treat FRDA, we examined transplantation of sensory neural progenitors derived from human embryonic stem cells (hESC) and FRDA induced pluripotent stem cells (iPSC) into adult rodent DRG regions. Our data showed survival and differentiation of hESC and FRDA iPSC-derived progenitors in the DRG 2 and 8 weeks post-transplantation, respectively. Donor cells expressed neuronal markers, including sensory and glial markers, demonstrating differentiation to these lineages. These results are novel and a highly significant first step in showing the possibility of using stem cells as a cell replacement therapy to treat DRG neurodegeneration in FRDA as well as other peripheral neuropathies.

Published
2021

21. If Human Brain Organoids Are the Answer to Understanding Dementia, What Are the Questions?

Author

Ooi, L, Dottori, M, Cook, AL, Engel, M, Gautam, V, Grubman, A, Hernández, D, King, AE, Maksour, S, Targa Dias Anastacio, H, Balez, R, Pébay, A, Pouton, C, Valenzuela, M, White, A, Williamson, R, Ooi, L, Dottori, M, Cook, AL, Engel, M, Gautam, V, Grubman, A, Hernández, D, King, AE, Maksour, S, Targa Dias Anastacio, H, Balez, R, Pébay, A, Pouton, C, Valenzuela, M, White, A, and Williamson, R

Published
2020

22. Molecular and Functional Characterization of Neurogenin-2 Induced Human Sensory Neurons

Author

Hulme, AJ, McArthur, JR, Maksour, S, Miellet, S, Ooi, L, Adams, DJ, Finol-Urdaneta, RK, Dottori, M, Hulme, AJ, McArthur, JR, Maksour, S, Miellet, S, Ooi, L, Adams, DJ, Finol-Urdaneta, RK, and Dottori, M

Abstract

Sensory perception is fundamental to everyday life, yet understanding of human sensory physiology at the molecular level is hindered due to constraints on tissue availability. Emerging strategies to study and characterize peripheral neuropathies in vitro involve the use of human pluripotent stem cells (hPSCs) differentiated into dorsal root ganglion (DRG) sensory neurons. However, neuronal functionality and maturity are limited and underexplored. A recent and promising approach for directing hPSC differentiation towards functionally mature neurons involves the exogenous expression of Neurogenin-2 (NGN2). The optimized protocol described here generates sensory neurons from hPSC-derived neural crest (NC) progenitors through virally induced NGN2 expression. NC cells were derived from hPSCs via a small molecule inhibitor approach and enriched for migrating NC cells (66% SOX10+ cells). At the protein and transcript level, the resulting NGN2 induced sensory neurons (NGN2iSNs) express sensory neuron markers such as BRN3A (82% BRN3A+ cells), ISLET1 (91% ISLET1+ cells), TRKA, TRKB, and TRKC. Importantly, NGN2iSNs repetitively fire action potentials (APs) supported by voltage-gated sodium, potassium, and calcium conductances. In-depth analysis of the molecular basis of NGN2iSN excitability revealed functional expression of ion channels associated with the excitability of primary afferent neurons, such as Nav1.7, Nav1.8, Kv1.2, Kv2.1, BK, Cav2.1, Cav2.2, Cav3.2, ASICs and HCN among other ion channels, for which we provide functional and transcriptional evidence. Our characterization of stem cell-derived sensory neurons sheds light on the molecular basis of human sensory physiology and highlights the suitability of using hPSC-derived sensory neurons for modeling human DRG development and their potential in the study of human peripheral neuropathies and drug therapies.

Published
2020

23. Particle-mediated delivery of frataxin plasmid to a human sensory neuronal model of Friedreich's ataxia.

Author

Czuba-Wojnilowicz, E, Viventi, S, Howden, SE, Maksour, S, Hulme, AE, Cortez-Jugo, C, Dottori, M, Caruso, F, Czuba-Wojnilowicz, E, Viventi, S, Howden, SE, Maksour, S, Hulme, AE, Cortez-Jugo, C, Dottori, M, and Caruso, F

Abstract

Increasing frataxin protein levels through gene therapy is envisaged to improve therapeutic outcomes for patients with Friedreich's ataxia (FRDA). A non-viral strategy that uses submicrometer-sized multilayered particles to deliver frataxin-encoding plasmid DNA affords up to 27 000-fold increase in frataxin gene expression within 2 days in vitro in a stem cell-derived neuronal model of FRDA.

Published
2020

24. Distribution of Particles in Human Stem Cell-Derived 3D Neuronal Cell Models: Effect of Particle Size, Charge, and Density

Author

Czuba-Wojnilowicz, E, Miellet, S, Glab, A, Viventi, S, Cavalieri, F, Cortez-Jugo, C, Dottori, M, Caruso, F, Czuba-Wojnilowicz, E, Miellet, S, Glab, A, Viventi, S, Cavalieri, F, Cortez-Jugo, C, Dottori, M, and Caruso, F

Abstract

Neurodegenerative diseases are generally characterized by a progressive loss of neuronal subpopulations, with no available cure to date. One of the main reasons for the limited clinical outcomes of new drug formulations is the lack of appropriate in vitro human cell models for research and validation. Stem cell technologies provide an opportunity to address this challenge by using patient-derived cells as a platform to test various drug formulations, including particle-based drug carriers. The therapeutic efficacy of drug delivery systems relies on efficient cellular uptake of the carrier and can be dependent on its size, shape, and surface chemistry. Although considerable efforts have been made to understand the effects of the physiochemical properties of particles on two-dimensional cell culture models, little is known of their effect in three-dimensional (3D) cell models of neurodegenerative diseases. Herein, we investigated the role of particle size (235-1000 nm), charge (cationic and anionic), and density (1.05 and 1.8 g cm-3) on the interactions of particles with human embryonic stem cell-derived 3D cell cultures of sensory neurons, called sensory neurospheres (sNSP). Templated layer-by-layer particles, with silica or polystyrene cores, and self-assembled glycogen/DNA polyplexes were used. Particles with sizes <280 nm effectively penetrated sNSP. Additionally, effective plasmid DNA delivery was observed up to 6 days post-transfection with glycogen/DNA polyplexes. The findings provide guidance in nanoparticle design for therapies aimed at neurodegenerative diseases, in particular Friedreich's ataxia, whereby sensory neurons are predominantly affected. They also demonstrate the application of 3D models of human sensory neurons in preclinical drug development.

Published
2020

25. More than a Corepressor: The Role of CoREST Proteins in Neurodevelopment

Author

Maksour, S, Ooi, L, Dottori, M, Maksour, S, Ooi, L, and Dottori, M

Abstract

The molecular mechanisms governing normal neurodevelopment are tightly regulated by the action of transcription factors. Repressor element 1 (RE1) silencing transcription factor (REST) is widely documented as a regulator of neurogenesis that acts by recruiting corepressor proteins and repressing neuronal gene expression in non-neuronal cells. The REST corepressor 1 (CoREST1), CoREST2, and CoREST3 are best described for their role as part of the REST complex. However, recent evidence has shown the proteins have the ability to repress expression of distinct target genes in a REST-independent manner. These findings indicate that each CoREST paralogue may have distinct and critical roles in regulating neurodevelopment and are more than simply "REST corepressors," whereby they act as independent repressors orchestrating biological processes during neurodevelopment.

Published
2020

31. Glomerular filtration rate: A prognostic marker in atrial fibrillation—A subanalysis of the AntiThrombotic Agents Atrial Fibrillation

Author

Proietti, Riccardo, Gonzini, Lucio, Pizzimenti, Giovanni, Ledda, Antonietta, Sanna, Pietro, Alturki, Ahmed, Russo, Vincenzo, Lencioni, Mauro, Siciliano, R., Boffa, M., Bazzanini, F., Di Nucci, G., Fonti, S., De Franceschi, T., Davio, P., Alagna, G., Cipollini, F., Arma, P., Gunnellini, M. G., Dottori, M., Paulillo, D., Giudice, M., Sicuro, M., Lenti, S., Iannelli, G., Notarstefano, P., Galiotto, M., Apolloni, Enzo, Molini, G., Massarelli, L., Di Iorio, P., Scandurra, F., Candelmo, F., Iodice, P., Laureano, R., Perlangeli, S., Praticò, A., Lucchesi, Q., Conese, V., Scalera, G., Palma, F., De Antoni, M. E., Beltramello, G., Carbonella, M., Capone, A., Bianchi, V., Zerella, F., Masina, M., Boggian, G., Pancaldi, L. G., Brucato, A. L., Scialfa, S., Ferrari, P., Gavazzi, A., Santoro, E., Bertinieri, G., Caragnano, V., Zaccaroni, S., Marchetti, G., Urbinati, S., Belmonte, G., Giannoni, C., Panuccio, D., Pedone, V., Colletta, M., Di Pasquale, G., Cemin, R., Paffoni, P. R. C., Pezzotti, Chiara, Capretti, M., Lamari, A. L., Maugeri, S., Moretti, R., Ganga, R., Mascia, P., Caddori, A., Cusumano, S., Alletto, M., DE VINCENZO, Ciro, Musacchio, E., Stendardo, A., Cantarella, SALVATORE ALFREDO, Ferrari, V., Bassano, F., PERRONE CAPANO, Carla, Piccinni, G. C., Catanzaro, M., Vinciguerra, A., Lusiani, L., De Caro, G., Scarcia, M., Scarcia, Aurora, Losi, E., Gaddi, O., Lo Sciuto, A., Cascio Ingurgio, N., Vignai, E., Romano, M., Borzì, V., Bellanuova, I. A., Felis, S., Gulizia, M. M., Francese, G. M., Artale, S., Mazzuca, S., Perticone, F., Tirotta, D., Talini, E., Ventrella, F., Iosa, G., Cuccurullo, O., Bertello, P. D., Benemio, G., Garognoli, O., Arcelli, G., Prosciutti, L., De Matthaeis, G., Quattrini, C., Calcagno, S., Canestrini, S., Franco, A., Pastorelli, R., Acquati, F., Botto, G. L., Sitta, N., Migliacci, R., Cosmi, F., Tarquini, B., Chiappetta, P., Sprovieri, M. F., Macrì, G., Bertolazzi, S., Spotti, Alessia, Pirelli, S., Marasco, M. F., Elia, Martina, Gambino, G. M., Fenoglio, L., Gelmini, G. P., Ziacchi, V., Rigon, N., Petix, N. R., Zipoli, A., Caiolo, A., Marino, E., Scattolin, G., Gerini, S., Parisi, G., Tavernese, G., Conti, Alessandro, Ferrante, Federico, Morettini, A., Alterini, B., Rocchi, Federico, Nozzoli, C., Goedecke, L., Seravalle, C., Cuomo, A., Panettieri, I., Pellegrino, P., Di Biase, M., Savarese, G., Patriarchi, F., Bondì, Giuseppina, Rossini, Elena, Nello, S., Ranieri, A. T., Gelonesi, F. N., Costantini, M., Dugnani, M., Ria, L., Mussardo, V., Zanini, G., Morgante, O., Fazio, G., Lo, G., Castello, C., Moroni, L. A., Costa, S., Domenicucci, S., Venzano, C., Loiacono, L., Ortuso, R., Esposito, L., Cuzzucrea, D. G., Fiammengo, F., Selva, E., Gestra, R., Alessandri, M., Nuzzi, G., Porrino, L., Parise, P., Capponi, E. A., Mandorla, S., Politi, Caterina, Olivieri, Claudia, Gurioli, L., Agostinelli, P., Striuli, R., Petrarca, Massimo, Corsini, Francesca, Orlandini, F., Badolati, S., Colarusso, D., Vertullo, V., Pelaggi, P., Campagna, G., Haupt, E., Parente, F., Milanese, G., Magliari, F., Morando, G., Guarise, P., Mazzone, A., Palumbo, G., Lambelet, P., Camaiti, A., Pasquinelli, P., Frediani, L., Vituliano, A., Brunelleschi, G., Lisi, C., La Torre, P. P. A., Villella, A., Rimoldi, A., Russo, V., Di Summa, F., Reggiani, A., Raimondo, F. C., Disalvo, D., Borrello, V. M., Magnante, A., Stellitano, E., Procopio, L., Franculli, F., Serafini, Filippo, Tondo, C., Fiorentini, C., Manfredini, R., Robbiolo, L., Pizzimenti, G., VASQUEZ LOPEZ, LUIDER FERNEY, Piangiamore, A., Tosi, P., Donà, G., Bacchiega, E., Malavasi, V., Modena, M. G., Divella, C., Marengo, C., Montanari, P., Manicardi, V., Abate, L., Cuccuini, A., Magni, S., Vincenti, A., Spinelli, M., Mortara, A., Specchia, G., Silvestri, N., Silvestri, Oriana, Piscopo, G., Muscherà, R., Gallucci, F., Cannavale, A., Bresciani, A., Perrone Filardi, P., Fontanella, Andrea, Iannuzzo, D., Lucà, S., Zuccoli, A., Rinaldi, P., Ferri, G., Barbieri, E., Grasselli, S., Rossi, A., Agosti, S., Sanna, GIAN PAOLO, Casu, G., Orecchioni, G., Da Silva Carvalho, P. C., POZZI MUCELLI, Roberto, Salvati, Fabio, Bendini, M. G., Giordano, G., Pellegrini, F., Pighini, G., Tremolada, F., Zanin, L., Ledda, A., Floresta, A. M., Enia, F., Nicolosi, G., Ingrillì, F., D'Angelo, A., Musacchio, D., Savastano, Silvia, Magnani, Leonardo, Capitelli, M., Cioni, Giovanni, Aloisi, B., De Finis, A., Vacri, A., Costantini, V., Guercini, F., Zingarini, G., Nardoni, M. C., Teghini, L., Panigada, G., Di Marco, S., Vergoni, W., Paonessa, K., Artom, A., Bigliardi, M., Riccardi, R., Riva, L., Marandino, A., Barsotti, L., Ginocchio, G., Marchese, Dario, Tintori, G., Annese, M., Breschi, R., Manini, M., Scopelliti, Giulia, Pastore, A., Spirito, G., Amato, A., Del Bianco, F., Ongari, M., Fiorencis, R., Querci, F., Martone, V. D., Molero, U., Fiusti, R., Giovannini, T., D'Arienzo, E., Cellamare, G., Placci, A., Gulli, G., Ruggeri, A., Pulitanò, G., Iori, I., Ingianni, N., Saporito, D., Marconi, GIAN MARIA, Grossi, Alice, Grosseto, D., Ciamei, M., Mete, F., Russo, F., Bianchi, C., Costantino, S., Manfellotto, D., Risa, M. P., Azzolini, P., Conversano, L., Santini, M., Macchiusi, A., Francia, P., Pietrantonio, F., Biscione, F., Magliano, G., Fedele, Francesca, Salituri, S., Salituri, F., Zamboni, S., Rossetti, C., Roncon, Leonora, Delucchi, M., De Benedictis, M., Vitolo, A., Anselmi, Michela, Celino, T., Moretti, V., Cuccurullo, M., Castelli, G., Martino, G., Pierandrei, G., Carella, A. M., Tonizzo, M., Nassi, R., Tarducci, R., Fronticelli Baldelli, M., Commisso, B., Lazzarini, D., Matarazzo, M. M., Novati, P., Petacchi, R., Maninchedda, P., Melandri, F., Bellesi, P., Sacchetti, C., Grandi, M., Cattana, A., Tassara, R., Menardo, G., Aykut, V., Chesi, G., Reverzani, A., Galgano, Angela, Bartone, B., Stornello, M., Muscio, G., Gemmiti, M. P., Alfonsi, F., Fontana, D., Astarita, C., Gaspardo, G., La Brocca, A., Rillo, M., Pascente, T., Pirozzi, M. R., Addis, L., De Siati, P., Beato, E., Iannaccone, V., Barabani, M., Castronuovo, M., Battaia, L., Biscottini, B., Boccali, A., Marengo, S., Dallerba, R., Diana, A., Coser, Alessandra, Pauletto, P., Calzolari, V., Olivari, Z., De Masi De Luca, G., Accogli, M., Gerloni, R., Cattin, Laura, Vitali Serdoz, L., Sinagra, G., Bulfoni, A., DE BIASIO, Melissa, Proclemer, A., Miserocchi, F., Marazzi, R., SALERNO URIARTE, JORGE ANTONIO, Levantesi, G., Olivetti, P., Capuano, A., Bertoncelli, M. C., Molinaro, N., Anastasio, L., Teti, G., Vescovo, G. A., Muriago, M., Incao, F., Lettica, G. V., Nieswandt, V., Osti, R., Tafi, A., Proietti, Riccardo, Gonzini, Lucio, Pizzimenti, Giovanni, Ledda, Antonietta, Sanna, Pietro, Alturki, Ahmed, Russo, Vincenzo, Lencioni, Mauro, Siciliano, R., Boffa, M., Bazzanini, F., Di Nucci, G., Fonti, S., De Franceschi, T., Davio, P., Alagna, G., Cipollini, F., Arma, P., Gunnellini, M. G., Dottori, M., Paulillo, D., Giudice, M., Sicuro, M., Lenti, S., Iannelli, G., Notarstefano, P., Galiotto, M., Apolloni, E., Molini, G., Massarelli, L., Di Iorio, P., Scandurra, F., Candelmo, F., Iodice, P., Laureano, R., Perlangeli, S., Praticò, A., Lucchesi, Q., Conese, V., Scalera, G., Palma, F., De Antoni, M. E., Beltramello, G., Carbonella, M., Capone, A., Bianchi, V., Zerella, F., Masina, M., Boggian, G., Pancaldi, L. G., Brucato, A. L., Scialfa, S., Ferrari, P., Gavazzi, A., Santoro, E., Bertinieri, G., Caragnano, V., Zaccaroni, S., Marchetti, G., Urbinati, S., Belmonte, G., Giannoni, C., Panuccio, D., Pedone, V., Colletta, M., Di Pasquale, G., Cemin, R., Paffoni, P. R. C., Pezzotti, C., Capretti, M., Lamari, A. L., Maugeri, S., Moretti, R., Ganga, R., Mascia, P., Caddori, A., Cusumano, S., Alletto, M., De Vincenzo, C., Musacchio, E., Stendardo, A., Cantarella, S. A., Ferrari, V., Bassano, F., Perrone, C., Piccinni, G. C., Catanzaro, M., Vinciguerra, A., Lusiani, L., De Caro, G., Scarcia, M., Scarcia, A., Losi, E., Gaddi, O., Lo Sciuto, A., Cascio Ingurgio, N., Vignai, E., Romano, M., Borzì, V., Bellanuova, I. A., Felis, S., Gulizia, M. M., Francese, G. M., Artale, S., Mazzuca, S., Perticone, F., Tirotta, D., Talini, E., Ventrella, F., Iosa, G., Cuccurullo, O., Bertello, P. D., Benemio, G., Garognoli, O., Arcelli, G., Prosciutti, L., De Matthaeis, G., Quattrini, C., Calcagno, S., Canestrini, S., Franco, A., Pastorelli, R., Acquati, F., Botto, G. L., Sitta, N., Migliacci, R., Cosmi, F., Tarquini, B., Chiappetta, P., Sprovieri, M. F., Macrì, G., Bertolazzi, S., Spotti, A., Pirelli, S., Marasco, M. F., Elia, M., Gambino, G. M., Fenoglio, L., Gelmini, G. P., Ziacchi, V., Rigon, N., Petix, N. R., Zipoli, A., Caiolo, A., Marino, E., Scattolin, G., Gerini, S., Parisi, G., Tavernese, G., Conti, A., Ferrante, F., Morettini, A., Alterini, B., Rocchi, F., Nozzoli, C., Goedecke, L., Seravalle, C., Cuomo, A., Panettieri, I., Pellegrino, P., Di Biase, M., Savarese, G., Patriarchi, F., Bondi, G., Rossini, E., Nello, S., Ranieri, A. T., Gelonesi, F. N., Costantini, M., Dugnani, M., Ria, L., Mussardo, V., Zanini, G., Morgante, O., Fazio, G., Lo, G., Castello, C., Moroni, L. A., Costa, S., Domenicucci, S., Venzano, C., Loiacono, L., Ortuso, R., Esposito, L., Cuzzucrea, D. G., Fiammengo, F., Selva, E., Gestra, R., Alessandri, M., Nuzzi, G., Porrino, L., Parise, P., Capponi, E. A., Mandorla, S., Politi, C., Olivieri, C., Gurioli, L., Agostinelli, P., Striuli, R., Petrarca, M., Corsini, F., Orlandini, F., Badolati, S., Colarusso, D., Vertullo, V., Pelaggi, P., Campagna, G., Haupt, E., Parente, F., Milanese, G., Magliari, F., Morando, G., Guarise, P., Mazzone, A., Palumbo, G., Lambelet, P., Camaiti, A., Pasquinelli, P., Frediani, L., Vituliano, A., Brunelleschi, G., Lisi, C., La Torre, P. P. A., Villella, A., Rimoldi, A., Russo, V., Di Summa, F., Reggiani, A., Raimondo, F. C., Disalvo, D., Borrello, V. M., Magnante, A., Stellitano, E., Procopio, L., Franculli, F., Serafini, F., Tondo, C., Fiorentini, C., Manfredini, R., Robbiolo, L., Pizzimenti, G., Vasquez, L., Piangiamore, A., Tosi, P., Donà, G., Bacchiega, E., Malavasi, V., Modena, M. G., Divella, C., Marengo, C., Montanari, P., Manicardi, V., Abate, L., Cuccuini, A., Magni, S., Vincenti, A., Spinelli, M., Mortara, A., Specchia, G., Silvestri, N., Silvestri, O., Piscopo, G., Muscherà, R., Gallucci, F., Cannavale, A., Bresciani, A., Perrone Filardi, P., Fontanella, A., Iannuzzo, D., Lucà, S., Zuccoli, A., Rinaldi, P., Ferri, G., Barbieri, E., Grasselli, S., Rossi, A., Agosti, S., Sanna, P., Casu, G., Orecchioni, G., Da Silva Carvalho, P. C., Pozzi, R., Salvati, F., Bendini, M. G., Giordano, G., Pellegrini, F., Pighini, G., Tremolada, F., Zanin, L., Ledda, A., Floresta, A. M., Enia, F., Nicolosi, G., Ingrillì, F., D'Angelo, A., Musacchio, D., Savastano, S., Magnani, L., Capitelli, M., Cioni, G., Aloisi, B., De Finis, A., Vacri, A., Costantini, V., Guercini, F., Zingarini, G., Nardoni, M. C., Teghini, L., Panigada, G., Di Marco, S., Vergoni, W., Paonessa, K., Artom, A., Bigliardi, M., Riccardi, R., Riva, L., Marandino, A., Barsotti, L., Ginocchio, G., Marchese, D., Tintori, G., Annese, M., Breschi, R., Manini, M., Scopelliti, G., Pastore, A., Spirito, G., Amato, A., Del Bianco, F., Ongari, M., Fiorencis, R., Querci, F., Martone, V. D., Molero, U., Fiusti, R., Giovannini, T., D'Arienzo, E., Cellamare, G., Placci, A., Gulli, G., Ruggeri, A., Pulitanò, G., Iori, I., Ingianni, N., Saporito, D., Marconi, M., Grossi, A., Grosseto, D., Ciamei, M., Mete, F., Russo, F., Bianchi, C., Costantino, S., Manfellotto, D., Risa, M. P., Azzolini, P., Conversano, L., Santini, M., Macchiusi, A., Francia, P., Pietrantonio, F., Biscione, F., Magliano, G., Fedele, F., Salituri, S., Salituri, F., Zamboni, S., Rossetti, C., Roncon, L., Delucchi, M., De Benedictis, M., Vitolo, A., Anselmi, M., Celino, T., Moretti, V., Cuccurullo, M., Castelli, G., Martino, G., Pierandrei, G., Carella, A. M., Tonizzo, M., Nassi, R., Tarducci, R., Fronticelli Baldelli, M., Commisso, B., Lazzarini, D., Matarazzo, M. M., Novati, P., Petacchi, R., Maninchedda, P., Melandri, F., Bellesi, P., Sacchetti, C., Grandi, M., Cattana, A., Tassara, R., Menardo, G., Aykut, V., Chesi, G., Reverzani, A., Galgano, A., Bartone, B., Stornello, M., Muscio, G., Gemmiti, M. P., Alfonsi, F., Fontana, D., Astarita, C., Gaspardo, G., La Brocca, A., Rillo, M., Pascente, T., Pirozzi, M. R., Addis, L., De Siati, P., Beato, E., Iannaccone, V., Barabani, M., Castronuovo, M., Battaia, L., Biscottini, B., Boccali, A., Marengo, S., Dallerba, R., Diana, A., Coser, A., Pauletto, P., Calzolari, V., Olivari, Z., De Masi De Luca, G., Accogli, M., Gerloni, R., Cattin, L., Vitali Serdoz, L., Sinagra, G., Bulfoni, A., De Biasio, M., Proclemer, A., Miserocchi, F., Marazzi, R., Salerno Uriarte, J. A., Levantesi, G., Olivetti, P., Capuano, A., Bertoncelli, M. C., Molinaro, N., Anastasio, L., Teti, G., Vescovo, G. A., Muriago, M., Incao, F., Lettica, G. V., Nieswandt, V., Osti, R., and Tafi, A.

Subjects
Male, medicine.medical_specialty, Time Factors, Clinical Investigations, Renal function, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Risk Factors, atrial fibrillation, glomerular filtration rate, mortality, Cardiology and Cardiovascular Medicine, Internal medicine, Antithrombotic, medicine, Humans, In patient, 030212 general & internal medicine, Renal Insufficiency, Cardiovascular mortality, Aged, Retrospective Studies, business.industry, Incidence, Atrial fibrillation, General Medicine, medicine.disease, Prognosis, Survival Rate, Italy, Hospital admission, Atrial Fibrillation, Female, Follow-Up Studies, Glomerular Filtration Rate, Morbidity, Cardiology, business
Abstract

OBJECTIVE: An increased cardiovascular mortality and morbidity has been widely reported in patients with atrial fibrillation (AF). In this study, a subanalysis of the AntiThrombotic Agents Atrial Fibrillation (ATA‐AF) is performed with the aim to evaluate estimated glomerular filtration rate (eGFR) as an independent prognostic marker of cardiovascular mortality and morbidity in patients with AF. METHODS AND RESULTS: The ATA‐AF study enrolled 7148 patients with AF, in 360 Italian centers. The eGFR was calculated from data reported in patient notes or hospital database. This post‐hoc analysis included 1097 AF patients with eGFR data available and 1‐year clinical follow‐up. The endpoint was assessed as cardiovascular mortality and/or hospital admission for cardiovascular causes at follow‐up. Patients were also divided in two groups according to the eGFR (

Published
2018

32. THE APEX TALKS…CARDIAC METASTASIS MIMICKING ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

Author

Maurizi, K, Lofiego, C, Vagnarelli, F, Capodaglio, I, Patani, F, Tofoni, P, Brugiatelli, L, Pietrucci, F, Dottori, M, Schicchi, N, Fogante, M, Esposto Pirani, P, Dello Russo, A, and Perna, G

Abstract

A 78–year–old man with a recent diagnosis of lung squamous cell carcinoma was referred to our cardiology department for marked ECG abnormalities (ST segment elevation in V2–V4 and T waves inversion in the antero–lateral leads, Fig.1) in the absence of ischemic symptoms and for the detection of an intramyocardial mass at the apical segments on the CT scan. He had no significant previous cardiovascular history. A transthoracic echocardiogram (TTE) was performed and showed an isoechoic mass at the LV apical segments measuring 3 x 4 cm apparently incorporating the myocardial wall without a clear cleavage plane (Fig.2a). The EF was normal. No pericardial effusion present. The contrast echocardiography with Sonovue revealed a late uptake of the contrast (Fig.2b). Cardiac magnetic resonance (CMR) showed an ovular image in the para–apical area of 40 x 23 cm consistent with a secondary lesion (Fig.3). Unfortunately, the exam was interrupted early due to a patient’s claustrophobic crisis, without having acquired the post–contrast images. Due to infiltrative appearance of the mass and the oncology history, this formation was highly suspicious for metastasis. No complicated ventricular arrhythmias were detected on ECG monitoring. No symptoms of heart failure were reported. Due to the marked EKG repolarization abnormalities the patient underwent coronary angiography which excluded significant stenosis. FDG PET/CT showed areas of increased metabolism also at liver and adrenal left gland. Finally, the patient was transferred to the oncology department for specific management. Cardiac metastases are more common than primary cardiac malignancy and are more frequently related to primary lung cancer, followed by breast cancer and hematologic malignancies. Typical presentation includes arrhythmias or conduction disturbances. The imaging findings of cardiac metastases are non–specific but mostly infiltrative, heterogeneous, and multiple masses may be present. Echocardiography is the initial imaging test for the detection of cardiac metastasis, although CMR, CT and PET/CT may be helpful. Herein we described a case of cardiac metastasis with EKG mimicking acute coronary syndrome. This finding is not uncommon among these patients. EKG findings of myocardial ischemia or injury, particularly localized and prolonged ST elevation, in the absence of ischemic symptoms have been reported in previous studies as high specificity for cardiac metastasis in patients with malignancy.

Published
2024
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33. Generation of Vestibular Tissue-Like organoids From Human Pluripotent Stem Cells Using the Rotary Cell Culture System

Author

Mattei, C, Lim, R, Drury, H, Nasr, B, Li, Z, Tadros, MA, D'Abaco, GM, Stok, KS, Nayagam, BA, Dottori, M, Mattei, C, Lim, R, Drury, H, Nasr, B, Li, Z, Tadros, MA, D'Abaco, GM, Stok, KS, Nayagam, BA, and Dottori, M

Abstract

Hair cells are specialized mechanosensitive cells responsible for mediating balance and hearing within the inner ear. In mammals, hair cells are limited in number and do not regenerate. Human pluripotent stem cells (hPSCs) provide a valuable source for deriving human hair cells to study their development and design therapies to treat and/or prevent their degeneration. In this study we used a dynamic 3D Rotary Cell Culture System (RCCS) for deriving inner ear organoids from hPSCs. We show RCCS-derived organoids recapitulate stages of inner ear development and give rise to an enriched population of hair cells displaying vestibular-like morphological and physiological phenotypes, which resemble developing human fetal inner ear hair cells as well as the presence of accessory otoconia-like structures. These results show that hPSC-derived organoids can generate complex inner ear structural features and be a resource to study inner ear development.

Published
2019

34. Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices

Author

Hyakumura, T, McDougall, S, Finch, S, Needham, K, Dottori, M, Nayagam, BA, Hyakumura, T, McDougall, S, Finch, S, Needham, K, Dottori, M, and Nayagam, BA

Abstract

Stem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed on target cell types. Nascent contacts between stem cells and hair cells were immunopositive for both synapsin I and VGLUT1, closely resembling expression of these puncta in endogenous postnatal auditory neurons and control cocultures. When hPSCs were cocultured with cochlear nucleus brainstem slice, significantly greater numbers of VGLUT1 puncta were observed in comparison to slice alone. New VGLUT1 puncta in cocultures with cochlear nucleus slice were not significantly different in size, only in quantity. This experimentation describes new coculture models for assessing auditory regeneration using well-characterised hPSC-derived neurons and highlights useful methods to quantify the extent of innervation on different cell types in the inner ear and brainstem.

Published
2019

37. Self-Organized Nanostructure Modified Microelectrode for Sensitive Electrochemical Glutamate Detection in Stem Cells-Derived Brain Organoids

Author

Nasr, B, Chatterton, R, Yong, JHM, Jamshidi, P, D'Abaco, GM, Bjorksten, AR, Kavehei, O, Chana, G, Dottori, M, Skafidas, E, Nasr, B, Chatterton, R, Yong, JHM, Jamshidi, P, D'Abaco, GM, Bjorksten, AR, Kavehei, O, Chana, G, Dottori, M, and Skafidas, E

Abstract

Neurons release neurotransmitters such as glutamate to communicate with each other and to coordinate brain functioning. As increased glutamate release is indicative of neuronal maturation and activity, a system that can measure glutamate levels over time within the same tissue and/or culture system is highly advantageous for neurodevelopmental investigation. To address such challenges, we develop for the first time a convenient method to realize functionalized borosilicate glass capillaries with nanostructured texture as an electrochemical biosensor to detect glutamate release from cerebral organoids generated from human embryonic stem cells (hESC) that mimic various brain regions. The biosensor shows a clear catalytic activity toward the oxidation of glutamate with a sensitivity of 93 ± 9.5 nA·µM-1·cm-2. It was found that the enzyme-modified microelectrodes can detect glutamate in a wide linear range from 5 µM to 0.5 mM with a limit of detection (LOD) down to 5.6 ± 0.2 µM. Measurements were performed within the organoids at different time points and consistent results were obtained. This data demonstrates the reliability of the biosensor as well as its usefulness in measuring glutamate levels across time within the same culture system.

Published
2018

38. Generation of Neural Organoids from Human Embryonic Stem Cells Using the Rotary Cell Culture System: Effects of Microgravity on Neural Progenitor Cell Fate

Author

Mattei, C, Alshawaf, A, D'Abaco, G, Nayagam, B, Dottori, M, Mattei, C, Alshawaf, A, D'Abaco, G, Nayagam, B, and Dottori, M

Abstract

Progress in aeronautics and spaceflight technologies requires in parallel further research on how microgravity may affect human tissue. To date, little is known about the effects of microgravity on human development. In this study we used the rotary cell culture system to investigate whether microgravity supports the generation and maintenance of neural organoids derived from human embryonic stem cells (hESCs) as a model of human brain development. Our results show that although neural organoids could be generated and maintained in microgravity conditions, there were changes in expression of rostral-caudal neural patterning genes and cortical markers compared to organoids generated in standard conditions. This phenomenon was also observed in hESC-derived cortical organoids exposed to microgravity for relatively shorter periods. These results are one of the first for analyzing human neurogenesis in a microgravity environment.

Published
2018

39. Phenotypic and Functional Characterization of Peripheral Sensory Neurons derived from Human Embryonic Stem Cells

Author

Alshawaf, AJ, Viventi, S, Qiu, W, D'Abaco, G, Nayagam, B, Erlichster, M, Chana, G, Everall, I, Ivanusic, J, Skafidas, E, Dottori, M, Alshawaf, AJ, Viventi, S, Qiu, W, D'Abaco, G, Nayagam, B, Erlichster, M, Chana, G, Everall, I, Ivanusic, J, Skafidas, E, and Dottori, M

Abstract

The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes that function to relay sensory stimuli, including temperature, pressure, pain and position to the central nervous system. Our knowledge of DRG sensory neurons have been predominantly driven by animal studies and considerably less is known about the human DRG. Human embryonic stem cells (hESC) are valuable resource to help close this gap. Our previous studies reported an efficient system for deriving neural crest and DRG sensory neurons from hESC. Here we show that this differentiation system gives rise to heterogeneous populations of sensory neuronal subtypes as demonstrated by phenotypic and functional analyses. Furthermore, using microelectrode arrays the maturation rate of the hESC-derived sensory neuronal cultures was monitored over 8 weeks in culture, showing their spontaneous firing activities starting at about 12 days post-differentiation and reaching maximum firing at about 6 weeks. These studies are highly valuable for developing an in vitro platform to study the diversity of sensory neuronal subtypes found within the human DRG.

Published
2018

40. Graphene foam as a biocompatible scaffold for culturing human neurons

Author

D'Abaco, GM, Mattei, C, Nasr, BK, Hudson, EJ, Alshawaf, AJ, Chana, G, Everall, IP, Nayagam, B, Dottori, M, Skafidas, E, D'Abaco, GM, Mattei, C, Nasr, BK, Hudson, EJ, Alshawaf, AJ, Chana, G, Everall, IP, Nayagam, B, Dottori, M, and Skafidas, E

Abstract

In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation.

Published
2018

41. AN ODD CASE OF GIANT INTRAPERICARDIAL MASS

Author

Maurizi, K, Vagnarelli, F, Lofiego, C, Capodaglio, I, Patani, F, Tofoni, P, Brugiatelli, L, Pietrucci, F, Dottori, M, Pupita, G, Schicchi, N, Fogante, M, Esposto Pirani, P, Dello Russo, A, and Perna, G

Abstract

A 70–year–old man was admitted to our emergency department (ED) for chest pain during the previous 3 days variable with breathing and chest movements. Clinical history included chronic coronary syndrome (2018: transient ST–segment elevation treated with PTCA + DES on proximal LAD), chronic kidney disease (CKD), chronic myeloid leukemia, chronic hepatitis B and C. At the ED an ECG showed atrial fibrillation (AF) with medium ventricular response (100 bpm). Transthoracic echocardiogram (TTE, Fig.1a, 1b, 1d) and transesophageal echocardiogram (TEE, Fig.1c) revealed a voluminous roundish iso–ipoechoic mass (“red star”) with regular and hyperechoic margin, apparently intrapericardial and close to the lateral wall of the left atrium, measuring 8 x 5.5 x 2 cm, without infiltrating the wall and without obstructing pulmonary veins return. Minimal pericardial effusion was present. On contrast TTE (Sonovue) there was no uptake of contrast agent (Fig.2a). The MRI (Fig.2b) showed a heterogeneous formation with slight late contrast enhancement consistent with intrapericardial hematoma. We submitted the case to cardiac surgeons who recommended close echocardiographic follow–up, given the absent hemodynamic impact of the mass. Management of pericardial hematoma in this clinical setting is controversial, it has limited available evidence, and thus there is significant variability in clinical practice. Due to AF, anticoagulant therapy with warfarin (imbricating with heparin) was initiated; anti–inflammatory treatment with ibuprofen and colchicine was prescribed. The patient was discharged in good general conditions. One month later we scheduled a follow–up visit with echo: a clear volumetric reduction of the intrapericardial hematoma was documented (Fig.3) and the patient reported a complete disappearance of the symptoms. We chose this case to highlight the importance of using all cardiac imaging techniques in the differential diagnosis of cardiac/pericardial masses; among others, MRI certainly represents the gold standard in this field but also Sonovue contrast echocardiography is definitely useful. Furthermore, a multidisciplinary approach involving clinical cardiologists, radiologists and cardiac surgeons is essential.

Published
2024
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42. Long-Distance Axonal Growth and Protracted Functional Maturation of Neurons Derived from Human Induced Pluripotent Stem Cells After Intracerebral Transplantation

Author

Niclis, JC, Turner, C, Durnall, J, McDougal, S, Kauhausen, JA, Leaw, B, Dottori, M, Parish, CL, Thompson, LH, Niclis, JC, Turner, C, Durnall, J, McDougal, S, Kauhausen, JA, Leaw, B, Dottori, M, Parish, CL, and Thompson, LH

Abstract

The capacity for induced pluripotent stem (iPS) cells to be differentiated into a wide range of neural cell types makes them an attractive donor source for autologous neural transplantation therapies aimed at brain repair. Translation to the in vivo setting has been difficult, however, with mixed results in a wide variety of preclinical models of brain injury and limited information on the basic in vivo properties of neural grafts generated from human iPS cells. Here we have generated a human iPS cell line constitutively expressing green fluorescent protein as a basis to identify and characterize grafts resulting from transplantation of neural progenitors into the adult rat brain. The results show that the grafts contain a mix of neural cell types, at various stages of differentiation, including neurons that establish extensive patterns of axonal growth and progressively develop functional properties over the course of 1 year after implantation. These findings form an important basis for the design and interpretation of preclinical studies using human stem cells for functional circuit re-construction in animal models of brain injury. Stem Cells Translational Medicine 2017;6:1547-1556.

Published
2017

43. No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism

Author

Lee, TT, Skafidas, E, Dottori, M, Zantomio, D, Pantelis, C, Everall, I, Chana, G, Lee, TT, Skafidas, E, Dottori, M, Zantomio, D, Pantelis, C, Everall, I, and Chana, G

Abstract

BACKGROUND: While evidence for white matter and astrocytic abnormalities exist in autism, a detailed investigation of astrocytes has not been conducted. Such an investigation is further warranted by an increasing role for neuroinflammation in autism pathogenesis, with astrocytes being key players in this process. We present the first study of astrocyte density and morphology within the white matter of the dorsolateral prefrontal cortex (DLPFC) in individuals with autism. METHODS: DLPFC formalin-fixed sections containing white matter from individuals with autism (n = 8, age = 4-51 years) and age-matched controls (n = 7, age = 4-46 years) were immunostained for glial fibrillary acidic protein (GFAP). Density of astrocytes and other glia were estimated via the optical fractionator, astrocyte somal size estimated via the nucleator, and astrocyte process length via the spaceballs probe. RESULTS: We found no evidence for alteration in astrocyte density within DLPFC white matter of individuals with autism versus controls, together with no differences in astrocyte somal size and process length. CONCLUSION: Our results suggest that astrocyte abnormalities within the white matter in the DLPFC in autism may be less pronounced than previously thought. However, astrocytic dysregulation may still exist in autism, even in the absence of gross morphological changes. Our lack of evidence for astrocyte abnormalities could have been confounded to an extent by having a small sample size and wide age range, with pathological features potentially restricted to early stages of autism. Nonetheless, future investigations would benefit from assessing functional markers of astrocytes in light of the underlying pathophysiology of autism.

Published
2017

44. Friedreich's ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency

Author

Crombie, DE, Curl, CL, Raaijmakers, AJA, Sivakumaran, P, Kulkarni, T, Wong, RCB, Minami, I, Evans-Galea, MV, Lim, SY, Delbridge, L, Corben, LA, Dottori, M, Nakatsuji, N, Trounce, IA, Hewitt, AW, Delatycki, MB, Pera, MF, Pebay, A, Crombie, DE, Curl, CL, Raaijmakers, AJA, Sivakumaran, P, Kulkarni, T, Wong, RCB, Minami, I, Evans-Galea, MV, Lim, SY, Delbridge, L, Corben, LA, Dottori, M, Nakatsuji, N, Trounce, IA, Hewitt, AW, Delatycki, MB, Pera, MF, and Pebay, A

Abstract

We sought to identify the impacts of Friedreich's ataxia (FRDA) on cardiomyocytes. FRDA is an autosomal recessive degenerative condition with neuronal and non-neuronal manifestations, the latter including progressive cardiomyopathy of the left ventricle, the leading cause of death in FRDA. Little is known about the cellular pathogenesis of FRDA in cardiomyocytes. Induced pluripotent stem cells (iPSCs) were derived from three FRDA individuals with characterized GAA repeats. The cells were differentiated into cardiomyocytes to assess phenotypes. FRDA iPSC- cardiomyocytes retained low levels of FRATAXIN (FXN) mRNA and protein. Electrophysiology revealed an increased variation of FRDA- cardiomyocyte beating rates which was prevented by addition of nifedipine, suggestive of a calcium handling deficiency. Finally, calcium imaging was performed and we identified small amplitude, diastolic and systolic calcium transients confirming a deficiency in calcium handling. We defined a robust FRDA cardiac-specific electrophysiological profile in patient-derived iPSCs which could be used for high throughput compound screening. This cell-specific signature will contribute to the identification and screening of novel treatments for this life-threatening disease.

Published
2017

45. Vaccine-related protection against PCV2 fetal infection in conventional gilts

Author

DARESTA, MARCO, FELICE, VIVIANA, PANARESE, SERENA, BIANCO, CARLO, BACCI, MARIA LAURA, SARLI, GIUSEPPE, OSTANELLO, FABIO, DOTTORI M., BONILAURI P., LELLI D., DARESTA M., FELICE V., PANARESE S., BIANCO C., BACCI M.L., DOTTORI M., BONILAURI P., LELLI D., SARLI G., and OSTANELLO F.

Subjects
REPRODUCTION, VACCINATION, SWINE, PCV2
Abstract

From previous investigations a low antibody titre and a prolonged viremia in non-vaccinated compared to vaccinated gilts revealed to be the higher risk factor associated to fetus infection in conventional animals inseminated with PCV2 spiked semen. A trial was performed to compare antibody titres, viremia, fetuses and fetal membranes/fluids samples PCV2 positivity in four groups of conventional gilts: 6 vaccinated with a commercial inactivated PCV2 vaccine (VAI), 6 vaccinated with a commercial vaccine based on a ORF2 capsid protein expressed in a baculovirus system and licensed for use in piglets (VBI), 6 non vaccinated (NVI) and 3 non-vaccinated and non-infected controls (CTR). Both types of vaccines were administered in gilts at 120 and 150 days of life. All animals received Regumate® for 18 days followed by an estrus syncronization and superovulation protocol. VAI, VBI and NVI groups were inseminated with a double (24 hrs apart) dose of PCV2 negative semen spiked with a PCV2b strain isolated in a PMWS outbreak in Italy. CTR gilts were fecundated with a double dose of PCV2 free semen. PCV2 in tissues was assessed and quantified by real time PCR. In the VAI group 4 out of 6 gilts were pregnant, in VBI 3 out of 6, in NVI 3 out of 6 and in CTR 2 out of 3, from which were collected 25, 19, 33 and 20 fetuses, respectively and corresponding placenta membranes and amniotic fluid. No differences in antibody titres nor viremia were revealed among groups during the trial. CTR showed the significantly (P

Published
2014

46. The Use of Forensic Entomology in Legal Veterinary Medicine: A Case Study in the North of Italy

Author

Dottori M, Rubini S, F. Defilippo, and Bonilauri P

Subjects
Veterinary medicine, Hermetia illucens, biology, Calliphora vicina, business.industry, Dermestes maculatus, fungi, biology.organism_classification, Dermestidae, Medicine, Carrion, Forensic entomology, Calliphoridae, business, Post-mortem interval
Abstract

During winter 2010 a forensic entomological study was undertaken in San Bartolomeo in Bosco (FE) Emilia-Romagna Region (North of Italy) on different animal carrion found in a farm several days after they died. The entomological evidence collected at the scene consisted of Calliphoridae (larvae of Calliphora vicina), Stratiomydae (larvae of Hermetia illucens), Dermestidae (larval exuviae of Dermestes maculatus). During diagnostic investigation the Diptera Larvae were taken from the carrion and were reared in the laboratory under constant temperature, humidity and fotoperiod. The minimum Post Mortem Interval (mPMI) was calculated using the quantity of thermal energy necessary for a given species to complete its life cycle from eggs to imago (accumulated degree-days-method). The results of the calculations were consistent with what the judicial investigation later showed. This case report illustrated the importance of using insects in legal veterinary medicine for define the time and circumstances of the death of an animal.

Published
2016

47. ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

Author

Busco, Susanna, Buzzoni, Carlotta, Mallone, Sandra, Trama, Annalisa, Castaing, Marine, Bella, Francesca, Amodio, Rosalba, Bizzoco, Sabrina, Cassetti, Tiziana, Cirilli, Claudia, Cusimano, Rosanna, De Angelis, Roberta, Fusco, Mario, Gatta, Gemma, Gennaro, Valerio, Giacomin, Adriano, Giorgi Rossi, Paolo, Mangone, Lucia, Mannino, Salvatore, Rossi, Silvia, Pierannunzio, Daniela, Tavilla, Andrea, Tognazzo, Sandro, Tumino, Rosario, Vicentini, Massimo, Vitale, Maria Francesca, Crocetti, Emanuele, Dal Maso, Luigino, Mazzoleni, G, Bulatko, A, Devigili, E, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Vittadello, F, Coviello, V, Cuccaro, F, Calabrese, A, Pinto, A, Cannone, G, Vitali, Me, Sampietro, G, Ghisleni, S, Giavazzi, L, Zanchi, A, Zucchi, A, Giacomin, A, Vercellino, Pc, Andreone, S, Fedele, M, Barale, A, Germinetti, F, Magoni, M, Zani, G, Salvi, O, Puleio, M, Gerevini, C, Adorni, A, Chiesa, R, Lonati, F, Tumino, R, Cascone, G, Frasca, G, Giurdanella, Mc, Martorana, C, Morana, G, Nicita, C, Rollo, Pc, Ruggeri, Mg, Spata, E, Vacirca, S, Sciacca, S, Sciacchitano, C, Fidelbo, M, Paderni, F, Benedetto, G, Vasquez, E, Bella, F, Calabretta, L, Castaing, M, Di Prima, A, Ieni, A, Leone, A, Pesce, P, Sciacchitano, S, Torrisi, A, Varvarà, M, Sutera Sardo, A, Mazzei, A, Lavecchia, Am, Mancuso, P, Nocera, V, Gola, G, Corti, M, Grandi, L, Caparelli, M, Mannino, S, Belluardo, C, Bizzoco, S, Davini, C, Lucchi, S, Villa, M, Anghinoni, E, Di Norcia, R, Ferretti, S, Biavati, P, Marzola, L, Migliari, E, Carletti, N, Petrucci, C, Brosio, F, Piccinni, L, Valente, N, Barchielli, A, Buzzoni, C, Caldarella, A, Corbinelli, A, Di Dia PP, Intrieri, T, Manneschi, G, Nemcova, L, Susini, N, Visoli, C, Zappa, M, Serraino, D, Angelin, T, Bidoli, E, Birri, S, Dal Maso, L, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Filiberti, Ra, Casella, C, Marani, E, Puppo, A, Celesia, Mv, Cogno, R, Garrone, E, Pannozzo, F, Busco, S, Rashid, I, Ramazzotti, V, Cercato, Mc, Natali, M, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Valerio, O, Melcarne, A, Quarta, F, Golizia, Mg, Raho, Am, De Maria, V, Vitarelli, S, Ricci, P, Guarda, L, Gatti, L, Pironi, V, Pasolini, A, Bordini, M, Autelitano, M, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Russo, Ag, Quattrocchi, M, Distefano, R, Panciroli, E, Bellini, A, Pinon, M, Spinosa, S, Spagnoli, G, Goldoni, Ca, Valla, K, Braghiroli, B, Cirilli, C, Donini, M, Amendola, V, Cavalieri d'Oro, L, Rognoni, M, Le Rose, L, Merlo, E, Negrino, L, Pezzuto, L, Fusco, M, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, Mf, Usala, M, Pala, F, Sini, Gm, Pintori, N, Canu, L, Demurtas, G, Doa, N, Vitale, F, Cusimano, R, Traina, A, Guttadauro, A, Cascio, Ma, Mannino, R, Ravazzolo, B, Brucculeri, Ma, Rudisi, G, Adamo, Ms, Amodio, R, Costa, A, Zarcone, M, Sunseri, R, Bucalo, G, Trapani, C, Staiti, R, Michiara, M, Bozzani, F, Sgargi, P, Borciani, E, Seghini, P, Faccini, F, Prazzoli, R, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Sacchettini, C, Ferrari, F, Roncaglia, F, Vicentini, M, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Caiazzo, Al, Cavallo, R, Colavolpe, Af, D'Alessandro, A, Iannelli, A, Lombardo, C, Senatore, G, Sensi, F, Cesaraccio, R, Sechi, O, Pirino, D, Mura, F, Contrino, Ml, Madeddu, A, Tisano, F, Muni, A, Dinaro, Y, Mizzi, M, Sacco, G, Aletta, P, Ziino, Ac, Maspero, S, Fanetti, Ac, Moroni, E, Cometti, I, Annulli, Ml, Cecconami, L, Minerba, S, Minicuzzi, A, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Sacchetto, L, Candela, G, Scuderi, T, Crapanzano, G, Taranto, V, Piffer, S, Gentilini, Ma, Rizzello, R, Cappelletti, M, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, Am, Solimene, C, Bianconi, F, Brunori, V, Tagliabue, G, Contiero, P, Tittarelli, A, Fabiano, S, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, di Grazia, L, Ruzza, Mr, Dei Tos AP, Baracco, M, Baracco, S, Bovo, E, Dal Cin, A, Fiore, Ar, Greco, A, Guzzinati, S, Monetti, D, Rosano, A, Stocco, C, Tognazzo, S, Zorzi, M, Merletti, F, Magnani, C, Pastore, G, Terracini, B, Alessi, D, Cena, T, Lazzarato, F, Macerata, V, Maule, M, Mosso, Ml, Sacerdote, C, Cocchioni, M, Pascucci, C, Ponz de Leon, M, Domati, F, Rossi, G, Kaleci, S, Rossi, F, Benatti, P, Roncucci, L, Di Gregorio, C, Magnani, G, Pedroni, M, Maffei, S, Mariani, F, Reggiani-Bonetti, L, Gennaro, V, Benfatto, L, Lando, C, Mazzucco, G, Romanelli, A, Storchi, C, Sala, O, Gabbi, C, and Buzzoni, C.

Published
2016

48. The advantage of women in cancer survival: An analysis of EUROCARE-4 data

Author

Micheli, A., Ciampichini, R., Oberaigner, W., Ciccolallo, L., de Vries, E., Izarzugaza, I., Zambon, P., Gatta, G., De Angelis, R., Hackl, M., Van Eycken, E., Verstreken, Martine, Holub, J., Jurickova, L., Storm, H. H., Engholm, G., Hakulinen, T., Belot, A., Hedelin, G., Velten, M., Tron, I., Le Gall, E., Launoy, G., Guizard, A. V., Faivre, J., Bouvier, A. M., Carli, P. M., Maynadie, M., Danzon, A., Buemi, A., Tretarre, B., Lacour, B., Desandes, E., Colonna, M., Molinie, F., Bara, S., Schvartz, C., Ganry, O., Grosclaude, P., Brenner, H., Kaatsch, P., Ziegler, H., Tryggvadottir, L., Comber, H., Berrino, F., Allemani, C., Baili, P., Sant, M., Sowe, S., Zigon, G., Tagliabue, G., Contiero, P., Bellu`, F., Giacomin, A., Ferretti, S., Serraino, D., Dal Maso, L., De Dottori, M., D. e. Paoli, A., Zanier, L., Vercelli, M., Orengo, M. A., Casella, C., Quaglia, A., Pannelli, F., Federico, M., Rashid, I., Cirilli, C., Fusco, M., Traina, A., De Lisi, V., Bozzani, F., Magnani, C., Pastore, G., Tumino, R., La Rosa, M. G., Spata, E., Sigona, A., Mangone, L., Falcini, F., Foca, F., Giorgetti, S., Senatore, G., Iannelli, A., Budroni, M., Patriarca, S., Zanetti, R., Rosso, S., Piffer, S., Franchini, S., Paci, E., Crocetti, E., La Rosa, F., Stracci, F., Cassetti, T., Guzzinati, S., Caldora, M., Capocaccia, R., Carrani, E., Francisci, S., Grande, E., Inghelmann, R., Lenz, H., Martina, L., Roazzi, P., Santaquilani, M., Simonetti, A., Tavilla, A., Verdecchia, A., Dalmas, M., Langmark, F., Bray, F., Johannesen, T. B., Rachtan, J., Gozdz, S., Siudowska, U., Mezyk, R., Bielska-Lasota, M., Zwierko, M., Pinheiro, P. S., Primic-Zakelj, M., Mateos, A., Torrella-Ramos, A., Zurriaga, Oscar, Marcos-Gragera, R., Vilardell, M. L., Izquierdo, A., Martinez-Garcia, C., Sanchez, M. J., Navarro, C., Chirlaque, M. D., Peris-Bonet, R., Ardanaz, E., Moreno, C., Galceran, J., Klint, A., Talback, M., Jundt, G., Usel, M., Frick, H., Ess, S. M., Bordoni, A., Luthi, J. C., Konzelmann, I., Probst, N., Lutz, J. M., Pury, P., Visser, O., Otter, R., Schaapveld, M., Coebergh, J. W. W., Janssen-Heijnen, M. L., Louis van der Heijden, Null, Greenberg, D. C., Coleman, M. P., Woods, Laura, Moran, T., Forman, D., Cooper, N., Roche, M., Verne, J., Mã¸ller, H., Meechan, D., Poole, J., Lawrence, G., Stiller, C., Gavin, A., Black, R. J., Brewster, D. H., Steward, J. A., Basque Country Cancer Registry, Vitoria-Gasteiz, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Public Health

Subjects
Oncology, Male, Pathology, Cancer Research, cancer survival - women, MESH : Age Distribution, MESH : Aged, MESH: Risk Assessment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH: Aged, 80 and over, Residence Characteristics, Neoplasms, 80 and over, Gender differences, Sex hormones, MESH: Neoplasms, MESH : Female, MESH: Residence Characteristics, Young adult, Age of Onset, MESH : Risk Assessment, MESH : Sex Distribution, MESH: Diagnosis-Related Groups, MESH: Aged, Aged, 80 and over, 0303 health sciences, education.field_of_study, MESH: Middle Aged, Relative survival, Thyroid, MESH: Sex Distribution, Middle Aged, MESH : Adult, 3. Good health, MESH : Age of Onset, Europe, MESH : Diagnosis-Related Groups, medicine.anatomical_structure, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, MESH : Residence Characteristics, Female, EUROCARE, Adult, medicine.medical_specialty, Adolescent, MESH: Age of Onset, MESH : Male, MESH : Sex Factors, Population, MESH : Europe, MESH : Young Adult, Rectum, Socio-culturale, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, 03 medical and health sciences, Young Adult, Age Distribution, Sex Factors, MESH: Sex Factors, SDG 3 - Good Health and Well-being, Internal medicine, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, Sex Distribution, education, MESH : Aged, 80 and over, MESH: Age Distribution, Survival analysis, Diagnosis-Related Groups, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, Cancer, Cancer survival, Survival Analysis, MESH: Adult, medicine.disease, MESH : Neoplasms, MESH: Male, MESH: Europe, Age of onset, MESH : Survival Analysis, business, MESH: Female
Abstract

We analysed 1.6 million population-based EUROCARE-4 cancer cases (26 cancer sites, excluding sex-specific sites, and breast) from 23 countries to investigate the role of sex in cancer survival according to age at diagnosis, site, and European region. For 15 sites (salivary glands, head and neck, oesophagus, stomach, colon and rectum, pancreas, lung, pleura, bone, melanoma of skin, kidney, brain, thyroid, Hodgkin disease and non-Hodgkin's lymphoma) age- and region-adjusted relative survival was significantly higher in women than men. By multivariable analysis, women had significantly lower relative excess risk (RER) of death for the sites listed above plus multiple myeloma. Women significantly had higher RER of death for biliary tract, bladder and leukaemia. For all cancers combined women had a significant 5% lower RER of death. Age at diagnosis was the main determinant of the women's advantage, which, however, decreased with increasing age, becoming negligible in the elderly, suggesting that sex hormone patterns may have a role in women's superior ability to cope with cancer. (C) 2008 Elsevier Ltd. All rights reserved.

Published
2009

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